1. Field of the Invention
The invention relates to a method for producing itaconic acid in high yields by fermentation with a yeast.
2. Description of the Prior Art
Itaconic acid (CAS #: 97-65-4) (methylenebutanedioic acid) is an α-substituted acrylic acid that is used in the manufacture of synthetic resins, coatings, and other industrial products (Tate, BE. Itaconic acid and derivatives. In Kirk-Othmer Encyclopedia of Chemical Technology, edn 3rd. Edited by Grayson M, Eckroth D: John Wiley & Sons; 1981. vol 13; and Willke T and Vorlop K D. Biotechnological production of itaconic acid. Appl Microbiol Biotechnol 2001; 56:289-295). It is produced commercially by the fungal fermentation of carbohydrates. The total market for itaconic acid has been quoted as being between 10,000 to 15,000 metric tons per year worldwide (Willke T, and Vorlop K D. Industrial bioconversion of renewable resources as an alternative to conventional chemistry. Appl Microbiol Biotechnol 2004; 66:131-142) with a price that is ten-times that of citric acid, a more widely used fermentation product (Bressler E and Braun S. Conversion of citric acid to itaconic acid in a novel liquid membrane bioreactor. Journal of Chemical Technology & Biotechnology 2000; 75:66-72).
The organism most often used for itaconic acid production is Aspergillus terreus, grown under phosphate-limited conditions (Willke & Vorlop, 2001, ibid; Roehr M and Kubicek C P. Further organic acids. In Biotechnology: Products of primary metabolism, edn 2. Edited by Roehr M: VCH Verlagsgesellschaft mbH; 1996:364-379. [Rehm H-J, Reed G (Series Editor): Biotechnology, vol 6]; and Lockwood L B: Production of organic acids by fermentation. In Microbial Technology, edn 2nd. Edited by Peppler H J, Perlman D: Academic Press; 1979:355-387. vol 1), although some species of the plant pathogenic fungal genus Ustilago, a basidiomycete, are also known to produce itaconic acid during fermentation (Willke & Vorlop, 2001, ibid). The sensitivity of A. terreus fermentations to metal concentrations (Lockwood, ibid) and difficulties working with filamentous organisms in bioreactors has led to the testing of yeasts for possible itaconic acid production. The patent literature in this area, reviewed by Willke and Vorlop (Willke & Vorlop, 2001, ibid), includes reports of itaconic acid production by a Candida mutant strain and Rhodotorula species. Tabuchi et al. (Itaconic acid fermentation by a yeast belonging to the genus Candida. Agricultural and Biological Chemistry 1981; 45:472-479) isolated a strain, putatively identified as a Candida, that produced itaconic acid at a 35% yield when grown under phosphate-limited conditions.
However, despite these advances, the need remains for an improved process for producing itaconic acid.